The present invention relates to optically active cephalosporin analogs and, more particularly, it pertains to optically active compounds of cephalosporin analogs represented by the general formula (I) ##STR1## wherein R.sub.1 represents a hydrogen or a protective group of carboxylic acid, Hal represents a halogen atom, and the hydrogens at the 6- and 7-positions have cis configuration, the pharmaceutically acceptable salts thereof and processes for producing the same.
The compounds represented by the general formula (I), (II), . . . may be named Compound [I], Compound [II], . . . , respectively.
Heretofore, a carbacephem compound, which is named according to the nomenclature in J. Am. Chem. Soc. 96. 7584 (1974), wherein the sulfur atom of cephalosporin is substituted with a carbon atom and which has a substituted methyl group at the 3-position is described in the above reference and J. Med. Chem. 20, 551 (1977). However, no compound of this type having especially strong antibacterial activity has been reported.
The present inventors have succeeded in preparing carbacephem compounds having various substituents at the 4-, 5- and 3-positions [The numbering system is as shown in the general formula (I)]. The compounds are described in the specifications of Japanese Patent Application (referred to as "JPA", hereinafter) Nos. 34696/78 [Japanese Published Unexamined Patent Application (referred to as "JPUPA", hereinafter) No. 128591/79] [German Offenlegungsschrift (referred to as "G.O." hereinafter) 2911786], 122403/78 (JPUPA No. 49376/80), 133072/78 (JPUPA No. 59186/80), 162005/78 (JPUPA No. 87788/80) and 8408/79 (JPUPA No. 100384/80), and U.S. patent application Ser. No. 23645.
Further, the present inventors have succeeded in preparing novel acylated carbacephems which are new antibiotics having strong antibacterial activities. These are described in JPA Nos. 34696/78 (JPUPA No. 128591/79), 122402/78 (JPUPA No. 49375/80), 127027/78 (JPUPA No. 53290/80), 133071/78 (JPUPA No. 59185/80), 162006/78 (JPUPA No. 87789/80), 162007/78 (JPUPA No. 87790/80), 162008/78 (JPUPA No. 87791/80), 8409/79 (JPUPA No. 100391/80), 92035/79 and 116720/79, G.O. 2911787, and U.S. patent application Ser. No. 23646, abandoned.
However, cephalosporin analogs mentioned above are prepared by synthetic methods using optically inactive staring compounds, and they are optically inactive dl [represented by (.+-.)] compounds unless they have optically active acyl group. More specifically, compounds represented by the general formula (I) wherein the hydrogen atoms at the 6- and 7-positions have cis configuration are present as a mixture of equal amounts of the mirror image compounds represented by the formulae (I-1) and (I-2) ##STR2## wherein R.sub.1 and Hal have the same significance as defined above.
The compounds represented by the general formula (IV) ##STR3## (wherein R.sub.4 represents a hydrogen, a lower alkyl group or a lower acyl group and R.sub.5 represents a hydrogen or a protective group of carboxylic acid) described in JPUPA No. 128591/79 are also present as a mixture of equal amounts of the mirror image compounds represented by the general formulae (IV-1) and (IV-2) ##STR4## wherein R.sub.4 and R.sub.5 have the same significance as defined above.
The present inventors have disclosed optically active compound of the compound represented by the general formula (IV) and method of producing the same in Japanese Patent Application No. 14533/79 (JPUPA No. 18872/80) wherein the optically active compound is defined as the compound represented by the general formula (IV-1).
The present inventors have succeeded in isolating and preparing one of the optically active mirror image compounds of the compound represented by the general formula (I) and completed the present invention. That is, the present inventors have first succeeded in preparing optically active compounds of cephalosporin analogs represented by the general formula (I) by optically selective deacylation reaction using an enzyme and an optically inactive dl compound having an acyl group as a starting compound. The desired compound is obtained in a remarkably high yield by the method.